Flaws In Breast Cancer Study

Inquiry Cites Eligibility, Patient Consent

June 05, 1994|By John Crewdson, Tribune Staff Writer.

Federal investigators have uncovered more disturbing irregularities in a landmark study of breast cancer treatment, including at least two cases in which women who were inappropriately given lumpectomies suffered recurrences of cancer soon after their operations.

A third woman received a lumpectomy despite what the investigators said was a lack of definitive evidence that she had cancer. Although the woman explicitly refused to participate in the lumpectomy study, her progress and condition were reported to study organizers until her death five years later from brain cancer.

A fourth woman, whose cancer was not removed entirely during surgery, was nonetheless enrolled in a branch of the lumpectomy study that denied her post-operative radiation therapy for treatment of the remaining malignancy.

"The standard approach is that this woman would have gone for chemotherapy first and then radiation afterwards," said Dr. Joseph Imperato, the chief of radiation oncology at Lake Forest Hospital. "I certainly would have recommended radiation, if they truly left disease behind."

Before she died, the woman accused her physician, a Los Angeles oncologist named David Plotkin, in a letter of having deprived her of informed consent by assuring her that radiation was not the "treatment of choice" for her condition.

The four women-none of whom, investigators said, should have been considered candidates for lumpectomies and all of whom are now dead-were enrolled during the early 1980s by Plotkin in what has since become one of the most influential studies in medical history.

The questions that are now being raised about whether any women were harmed by enrollment in that study, the investigators said, would not have arisen "if only eligible patients were entered" in the study by Plotkin, "and if the data entered on these patients had been correct."

Plotkin's patients were among more than 2,000 women enrolled in Protocol B-06, headquartered at the University of Pittsburgh and designed as the definitive comparison of mastectomy with the less-disfiguring operation commonly known as lumpectomy. Although the study concluded that lumpectomy was no riskier than mastectomy for women with early stage breast cancers, recent revelations that some study data was falisfied or is otherwise inaccurate have led to concerns about whether the conclusion remains entirely valid.

Two weeks ago, citing "serious concerns about the reliability" of data from the Memorial Cancer Research Foundation of Southern California, which Plotkin heads, the National Cancer Institute placed an embargo on any further federal research funding for Plotkin and ordered his termination as a principal investigator for the breast cancer study. The NCI directed that another physician take charge of following up the 200 or so patients enrolled by Plotkin over the past two decades in the lumpectomy and other breast cancer studies.

The NCI investigation was requested by Plotkin, in anticipation of an article in the Tribune last month reporting numerous apparent irregularities in the lumpectomy data collected by his foundation. Nearly all the Tribune's findings are confirmed by the NCI's 45-page account of its investigation, which also contains several serious discrepancies not mentioned in the article.

"Would I in any way falsify any records? Absolutely not," Plotkin told the Tribune in April. "But the human stuff-are there mistakes in my records? You bet." He attributed many of the mistakes to errors by the succession of part-time data managers he has employed over the years.

The federal Office of Protection from Research Risks, which is charged with protecting the rights of human subjects in medical research, is investigating Plotkin's decision to permit a Tribune reporter to examine some of his research records, which the NCI report termed "a severe breach of patient confidentiality."

The NCI investigators stressed that their findings were only preliminary because they had been unable to examine primary medical records for more than half the 29 patients Plotkin enrolled in the lumpectomy study. The investigators said they were hampered by the fact that many of the patients were not Plotkin's, but were recruited by him through a network of oncologists and surgeons across Southern California.

The investigators nevertheless concluded that Plotkin's contribution to the lumpectomy study had been marred by "a low overall quality of clinical research" related to the eligibility of the patients, the haphazard follow-up of their progress, and the questionable means by which their informed consent was obtained.